Many serious diseases of both humans and animals are caused by abnormal physical-state transition of benign or beneficial substances, normally present in the body, such that a disease-causing substance results. Discovery of conditions, compounds, or compositions that prevent or inhibit formation or that reverse formation (e.g., promote dissolution or destruction) of such disease-causing substances is an important part of pharmaceutical development and research. Also important is discovery of compounds, compositions, or conditions that promote desirable physical-state transitions for reversal of disease processes, for example, reversal of osteoporosis by inducing formation of bone mass.
These so-called physical-state-transition disorders are a large and very heterogenous group of diseases. They include disorders caused by undesirable crystallization, bio-mineralization, polymerization, or calculus build up, such as bladder stones, kidney stones, gall stones, tartar build up on teeth, protein precipitation in body fluids, passage of aggregates based on their form or habit, and defects in bone formation or loss of bone mass. Polymerization, multimerization, and macro-molecular structures are significant in diseases, disorders, and conditions such as cancer and metastasis, allergy, e.g., due to IgE complexes, malarial parasite infections with sequestration of hematin, assembly of viral capsids and the like. Additionally, it is now known that structure or conformation changes of proteins are the cause or contribute to a range of very serious human diseases such as Alzheimer's disease, the amyloid diseases, and the prion diseases, such as Creutzfeldt-Jakob Disease.
The occurrence of these undesirable physical-state transitions can be influenced by the immediate environment. For example, the deposition of calcium phosphate in solid form can be inhibited by the presence of pyrophosphate, even if the local concentration of calcium and phosphate ion would promote such deposition. Likewise, the formation of solids in the urinary system can be altered by controlling the pH of the urine or by preventing nucleation. The tendency of protein to adopt a beta-pleated sheet conformation, typical of the amyloid diseases, is critically dependent on the precise environmental conditions.